Although many patients with bipolar depression remain symptomatic despite
the use of mood stabilizers, the effectiveness and risk of adding an
antidepressant to their medication regimen remains controversial. A study in
the September American Journal of Psychiatry adds weight to the
opinion that, at least for a subpopulation of patients who have simultaneous
manic symptoms and full-blown depression, adjunctive antidepressants provide
few benefits and may even exacerbate mania.
The study was based on the naturalistic treatments and patient outcomes
collected in the nonintervention phase of the Systematic Treatment Enhancement
Program for Bipolar Disorder (STEP-BD) study, in which practitioners were
given no particular guidelines regarding adjunctive antidepressants.
Specifically, the researchers investigated whether antidepressants plus
standard mood stabilizers succeeded in bringing patients out of a depressive
episode faster than mood stabilizers alone.
STEP-BD, which was funded by the National Institute of Mental Health and
conducted between 1998 and 2005, is the largest national research program on
the treatment of patients with bipolar disorder. It sought to clarify
treatment effectiveness and patients' disease course and outcomes in real-life
clinical settings. The study design included both naturalistic treatment
components and randomized, controlled, interventional treatments. (See related
article Psychosocial Benefits Accrue When Psychotherapy Part of
Among the first 2,000 patients enrolled in the naturalistic phase of
STEP-BD, the authors chose a subgroup of 335 patients taking mood stabilizers
who met the DSM-IV criteria for a full depressive episode while also
having two or more manic symptoms. Patients with depression and subsyndromal
mania were included because they were more likely to be prescribed an
antidepressant than those who met the diagnosis of mixed episode, the authors
said. About half of the patients in the subgroup (145) were treated with an
adjunctive antidepressant before or at the time of enrollment; the remainder
The time to recovering (defined as four weeks of two or fewer unequivocally
present affective symptoms) or recovery (eight weeks of two or fewer affective
symptoms) was not significantly different between patients taking an
antidepressant with a mood stabilizer and those taking a mood stabilizer only.
In other words, the addition of an antidepressant did not hasten patient
recovery from a depressive episode.
The authors then expanded their analysis to a total of 445 patients with
bipolar depression and any number of manic symptoms at baseline as well as
those with no manic symptoms. For those who had one or more manic symptoms at
baseline, adding an antidepressant was significantly associated with increased
severity of mania (measured by the Young Mania Rating Scale) at the
three-month follow-up visit.
STEP-BD researchers led by Gary Sachs, M.D., of the Department of
Psychiatry at the Massachusetts General Hospital/Harvard University Medical
School had found in another study that giving antidepressants to patients who
had bipolar depression but no concomitant manic symptoms and were already on
mood stabilizers increased neither the percentage of patients who achieved
recovery nor their risk of switching to mania, compared with patients taking
only mood stabilizers (New England Journal of Medicine, April
That study "found that antidepressants neither help nor harm these
bipolar patients in a more 'pure' depressive episode who had no manic
symptoms. Our study looked at a different group of patients with depression
plus manic symptoms," said Joseph Goldberg, M.D., the lead author of the
current American Journal of Psychiatry study and director of the
Affective Disorders Program at Silver Hill Hospital in New Canaan, Conn., in
an interview with Psychiatric News.
"In previously collected data, we had found that about half of
patients with bipolar depression had subsyndromal mania that does not meet the
DSM-IV definition of a mixed episode, while only a third had 'pure'
depression without manic symptoms." These data were presented at APA's
2007 annual meeting.
Despite the lack of evidence clearly supporting their advantages,
antidepressants are widely prescribed to bipolar patients experiencing a
depressive episode, as Ross Baldessarini, M.D., and colleagues reported in the
January Psychiatric Services. This finding may reflect the difficulty
in detecting manic symptoms when depression is the predominant feature.
In addition, long-term observational data published by Lewis Judd, M.D., of
the Department of Psychiatry at the University of California, San Diego, and
colleagues in the Archives of General Psychiatry (June 2002 and
December 2005) have shown that depressive episodes and symptoms consume a much
larger portion of patients' lives and cause more disability and mortality than
do manic symptoms.
Goldberg and colleagues pointed out in their article that"
practitioners often fail to recognize manic symptoms during bipolar
mixed states" or "underappreciate manic or hypomanic
symptoms" during depressive episodes. They suggested that psychiatrists
should be more vigilant in detecting signs of mania during a depressive
episode that are below the threshold of DSM-IV-defined mixed
Even if a patient is clearly experiencing a depressive episode, the
clinician "should be conscientious of any concomitant manic
symptoms," Goldberg recommended. "One should be very cautious with
the use of antidepressants in these patients."
"Adjunctive Antidepressant Use and Symptomatic Recovery Among
Bipolar Depressed Patients With Concomitant Manic Symptoms: Findings From the
STEP-BD" is posted at<http://ajp.psychiatryonline.org/cgi/content/full/164/9/1348>.▪